ANN ARBOR, Mich.
- Early-stage prostate cancer patients with the most aggressive
form of the disease may benefit more from high doses of carefully
delivered radiation than previous reports would suggest, a
new multi-center study led by current and former University
of Michigan Comprehensive Cancer Center researchers has found.

In fact, the study showed that X-rays delivered to the exact
three-dimensional location of 180 high-risk tumors kept 79
percent of early-stage patients cancer free for at least five
years -- a remarkable improvement over the usual 50-percent
recurrence rate for those who have their prostates removed
or have lower-dose radiation therapy.

The study, which shows a clear positive effect from higher
doses, is published in the current issue of the International
Journal of Radiation Oncology, Biology and Physics. It adds
to years of U-M research into lower radiation doses for less-severe
prostate cancer and other tumors.

The research involved only patients with rarer but more often
deadly forms of prostate cancer. But its results suggest that
higher doses of 3-D conformal radiation, as it is called,
may help prostate cancer patients with less-dangerous types
of the disease, says study senior author Howard Sandler, M.D.,
associate professor and associate chair of radiation oncology
in the U-M Health System.

"This new evidence of an advantage from higher doses
not only validates the use of this approach in this subgroup
of high-risk patients, it also hints strongly that lower-grade
tumors could be vulnerable to increased radiation delivered
with careful planning," says Sandler.

Sandler and former U-M fellow John Fiveash, M.D., now at
the University of Alabama-Birmingham, teamed with other researchers
from the U-M the Fox Chase Cancer Center in Pennsylvania and
the University of California, San Francisco to pool data for
the study.

They looked back at how well patients with the highest-grade
kinds of tumors did after treatment with radiation doses as
much as ten percent more intense than conventional levels.
As with all 3-D conformal radiation therapy, patients received
the doses after high-resolution images of their individual
tumors allowed doctors to plot the best angles for aiming
the radiation beam at the tumor's exact outline, while skirting
important normal tissue like the bladder and hip bones.

3-D conformal radiation therapy was pioneered clinically
in the mid-1980s at the U-M and elsewhere under the leadership
of radiation oncology researchers like Allen Lichter, M.D.,
now dean of the U-M Medical School. It combines recent advances
in medical imaging, which allow 3-D images to be made of the
body with high resolution, with sophisticated radiation equipment
that can produce many thin beams of intense X-rays and aim
them with pinpoint accuracy. It has few side effects.

Physicians can look at a virtual representation of a tumor
with a "beam's eye view" that shows them the irregular
cross-section shape of each patient's cancer and predicts
exactly where each beam of radiation will pass through the
body. Then, using planning software, careful patient positioning
and specially designed shutters for the X-rays to pass through,
they can generate a combination of beams from different angles
that will intersect when they reach the tumor. "This
delivers a combined dose of radiation powerful enough to kill
cancer cells, even though the individual beams leave nearby
normal tissue relatively unscathed," says Sandler.

The U-M has used 3-D conformal radiation therapy for more
than a decade as standard radiation therapy. Now, studies
such as this one aim to optimize its effectiveness by studying
what happens when radiation dose to the tumor is carefully
stepped up. Meanwhile, U-M researchers are developing the
next generations of hardware and software to make radiation
delivery even more precise and harmless to non-cancerous tissue
than it already is.

The new study looked at the survival time and cancer-free
time -- defined as the period in which patients' blood showed
no increase in prostate-specific antigen, or PSA -- of patients
whose cancer cells showed microscopic evidence of being especially
aggressive.

Pathologists rate tumor biopsy samples from 1 to 10 on what
is known as the Gleason scale, which ranks "normal"
looking cells low and gives higher scores to more abnormal-looking
ones which have the potential to grow out of control. All
patients in the study had the highest Gleason ratings, from
8 to 10 -- ratings that appear relatively rarely among all
prostate cancer patients but disproportionately among the
39,000 men who die from the disease each year.

In addition to Gleason score, which rates the tumor's growth
potential, the study also looked at the stage of each patient's
cancer at the time of radiation therapy. Stages, ranging from
1 to 4, rate how far the cancer has spread within, around
and beyond the prostate.

Patients in the study received radiation almost daily for
several weeks, resulting in doses that ranged from the currently
conventional -- around 66-70 Gray, or Gy -- all the way up
to 80 Gy. Even though the difference in dose sounds small,
the increase in radiation effect upon the tumor is large.

Of the 180 patients, 61 percent had a Gleason score of 8,
and 57 percent had stage 1 or 2 cancer. Their average age
was 72, and follow-up time averaged three years but ranged
up to 8 years. Some patients took hormone-reducing drugs as
well, though no effect was seen.

In all, 62.5 percent stayed within PSA limits, showing no
recurrence of their cancer, for five years, and 67.3 percent
survived five years. But, Sandler says, "the most dramatic
effect was seen in stage 1 or 2 patients with lower pre-treatment
PSA levels who received the highest radiation doses -- suggesting
that the therapy works best for those who catch their aggressive
cancer early. By comparison, recent examinations of conventional
radiation therapy and surgery have shown recurrence rates
higher than originally thought."